A role for galanin transmission in central respiratory chemoreception following acute and chronic respiratory challenge.
(2017) Society for Neuroscience (SfN) — Location: Washington DC, USA
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- Abstract
- Abstract: Glutamatergic chemoreceptor neurons in the retrotrapezoid nucleus (RTN) form extensive projections to the ventral respiratory column (VRC), which generates the rhythmic breathing pattern. RTN chemoreceptors are critically involved in mediating the central respiratory chemoreflex, which is the primary homeostatic mechanism used by mammals to control blood CO2 levels. Although glutamate is the primary transmitter used to excite the VRC (Holloway BB et al 2015, Ruffault PL et al 2015), 50% of RTN neurons in the rat also express the inducible neuropeptide transmitter galanin (Stornetta et al 2009, Spirovski et al 2012). Previous studies have demonstrated that injection of galanin into the VRC has an inhibitory effect on breathing, inducing apnoea (Abbott SB et al 2009). Importantly galanin also attenuated the ventilatory reflex responses to hypoxia and hypercapnia (elevated CO2). We hypothesise that RTN galanin signalling acts as a gain-control mechanism for the central chemoreflex, and that neuropeptide expression is regulated by environmental signals (such as blood pH). We aimed first to determine the distribution of preprogalanin (ppGal) mRNA in the mouse RTN using in situ hybridisation (ISH). We also aimed to determine whether ppGal mRNA expression is altered in the RTN, VRC or cerebellum following hypoxic or hypercapnic respiratory challenge. Chronic intermittent hypoxia challenge: Rat pups (p7) were divided into normoxia (control, 21%O2/79% N2) and intermittent hypoxia (IH, 8% or 12% O2, balance N2) groups. Rat pups in IH groups were exposed to a hypoxic environment for an hour each day, for 5 days. Short term hypercapnia challenge: Adult mice were divided into normoxia (control , 0% CO2) and hypercapnia (5% CO2, balance room air) groups. Mice in the hypercapnia group were exposed to a single 5% CO2 challenge for 3, 6 or 8 hours. Following the challenge, animals were euthanized and fresh tissues (RTN, VRC, and cerebellum) were isolated. We assessed changes in gene expression with quantitative PCR (QPCR). The ISH results show that ~30% of mouse RTN neurons are galaninergic (ppGal+). QPCR results show that there was no significant change in RTN ppGal mRNA levels following IH (12% O2), however, ppGal was upregulated 2-fold in the RTN and 3-fold in the VRC following 8% O2, compared to normoxia. Preliminary data suggests that ppGal mRNA is downregulated in the RTN following a 3, 6 and 8 hour hypercapnia challenge, compared to control conditions. Overall, our data suggest a role for galanin transmission in RTN chemoreception following acute and chronic respiratory challenge which may occur in respiratory syndromes including COPD and sleep apnea.
- Affiliations
University of New South Wales
Citations
Kumar, N. N., Dereli, A., Bayliss, D., & Jones, N. (2017). A role for galanin transmission in central respiratory chemoreception following acute and chronic respiratory challenge. Society for Neuroscience (SfN), Washington DC, USA.